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Dysfunction of the salivary gland in NOD mouse

Research Project

Project/Area Number 07672199
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionTsurumi University

Principal Investigator

NAKAGAWA Yoichi  Tsurumi University, School of Dental Medicine, Lecturer, 歯学部, 講師 (90148057)

Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsSjogren's syndrome / NOD mouse / salivary gland / signal transduction / neuropeptide / Insulin-like growth factor / 唾液腺機能 / 自己免疫疾患 / 糖尿病 / Insulin-like Growth Factor / IGF-binding protein / 組織内濃度 / ムスカリン受容体 / cAMP / イノシトール / 自己抗体
Research Abstract

The non-obese diabetic (NOD) mouse has been recognized as an animal model for autoimmune type 1 insulin-dependent diabetes mellitus and has been shown a loss in secretory function of the salivary glands. To understand the salivary functional changes of the salivary gland in NOD mouse, the following investigations were carried out.
(1) The secretory response to muscarinic receptor stimulation : NOD showed a reduced potential for the generation of cAMP in the glands. Basal and agonist stimulated concentrations of inositol phosphate were reduced in submandibular gland of NOD mice. The receptor density was decreased in the glands. The reduction of muscarinic agonist response was suggested to be due to a generalized reduction in signal transduction components as a consequence of autoantibodies detected against cell surface antigens.
(2) The levels of neuropeptides and salivary gland responses : Injection of either of the three neuropeptides, substance P (SP), vasoactive intestinal polypeptide … More (VIP), and neuropeptide Y (NPY), in combination with the muscarinicchorinergic agonist pilocarpine increased saliva flow rates in Balb/c mice while threr was no observable augmentation to flow rates in NOD mice. Radioimmunoassay determination of neuropeptide concentrations in the submandibular and parotid glands revealed reduced levels of SP with diabetic onset. VIP concentrations were reduced in the submandibular gland of NOD mice. The findings suggested the dysfunction observed in NOD mice to be due to a general loss of neurotransmitter responsiveness on the part of salivary gland cells.
(3) Gastrointestinal absorption of Insulin-like growth factor (IGF) and the levels of Insulin-like growth factor binding protein (IGFBP) : IGFBP were detected in the sera, but not in the saliva. Gavage administration of radiolabeled IGF indicated substantial uptake from the gastrointestinal tract and significant tissue distribution. The tissue distribution in the diabetic NOD mouse was reduced, which suggest to contribute to reduced growth and wound healing potentials. Less

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Yamamoto, H., et al.: "Alteration in the secretory response of non-obese diabetic(NOD)mice to muscarinic receptor stimulation." Clinical Immunology and Immunopathology. 78(3). 245-255 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamamoto, H., et al.: "Detection of alterations in the levels of neuropeptides and salivary gland responses in the non-obese diabetic mouse model for autoimmune sialoadenitis." Scand J immunol. 45. 55-61 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakagawa, Y., et al.: "Gastrointeistinal absorption of Insulin-like growth factor in the mouse in the absence of salivary Insulin-like growth factor binding protein." Biochemical Pharmacology. 53(2). 233-240 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamamoto, H., Sims, E.S., Macauley, S.P., Nguyen, K-H.T., Nakagawa, Y.and Humphreys-Beher, M.G.: "Alteration in the secretory response of non-obese diabetic (NOD) mice to muscarinic receptor stimulation." Clinical Immunology and Immunopathology. 78(3). 245-255 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamamoto, H., Ishibashi, K., Nakagawa, Y., Maeda, N., Zeng, T., Robinson, C.P., Oxford, g.E., Chegini, N.and Humphreys-Beher, M.G.: "Detection of alterations in the levels of neuropeptides and salivary gland responses in the non-obese diabetic mouse model for autoimmune sialoadenitis." Scand J Immunol. 45. 55-61 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakagawa, Y., Oxford, G.E., Ishibasih, K., Yamamoto, H., Maeda, N., Bowen, E., Brayr, J., and Humphreys-Beher, M.G.: "Gastrointeistinal absorption of Insulin-like growth factor in the mouse in the absence of salivary insulin-like growth factor binding protein." Biochemical Pharmacology. 53. 233-240 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamamoto,H.et al.: "Detection of alterations in the levels of neuropeptides and salivary gland responses in the non-obese diabetic mouse model for autoimmune sialoadenitis." Scand J immunol. 45. 55-61 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] NAKAGAWA,Y: "Gastrointestinal absorption of Insulin-like growth factor in the mouse in the absence of salivary Insulin-like growth factor binding protein" Biochemichal pharmacology. 53・2. 233-240 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] YAMAMOTO,H: "Alterations in the secretory response of Non-obese diabetic (NOD) mice to muscarinic receptor stimulation" Clinical Immunology and Immunopathology. 78・3. 245-255 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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